Diffusion Tensor Imaging (DTI), proton MR Spectroscopy (MRS) and MR Spectroscopic Imaging (MRSI) will be used to study in vivo microstructural and biochemical characteristics of the brain in chronic alcoholics compared with controls. DTI yields measures of the diffusion of tissue water (apparent diffusion coefficient [ADC]) and directional coherence of white matter fibers (fractional anisotropy [FA]). MRS provides quantitative measures of several brain metabolites, including N-acetyl compounds (NAc), primarily N-acetyl-aspartate, a marker of living, mature neurons; creatine+phosphocreatine (Cr), a reflection of high-energy phosphate metabolism; choline (Cho), an index of membrane turnover; and myo-inositol (mI), an index of neuronal degeneration. Measurement of these indices of brain deterioration and recovery at different times in the course of abstinence and resumed drinking should provide clues to mechanisms underlying both permanent and reversible brain changes associated with alcoholism. Candidate processes include reversible de-and remyelination along with axonal regression and recovery and the permanent processes of neuronal and axonal degeneration. Specific Aims are: 1) To use DTI and single voxel MRS to examine white matter fiber integrity in alcoholics at 3 times post-detoxification-1, 4, and 26 weeks. At 26 weeks 50% of the alcoholics will have remained abstinent and 50% will have relapsed. We will test the following hypotheses: a) between weeks 1 and 4 alcoholics, relative to controls, will show increases in white matter FA and NAc and decreases in ADC, Cho and mI, even though white matter volume changes may not be detectable; b) between weeks 4 and 26, alcoholics who abstain will show increases in white matter volume, FA and NAc concentration whereas those who relapse will show decreases in white matter volume, FA and NAc and increases in ADC, Cho and mI. 2) To use MRSI to examine gray matter and white matter metabolite concentrations in longer-term abstinent alcoholic men and women. We will test the hypothesis that longer-term abstinent alcoholics will exhibit residual gray and white matter deficits, greatest in the frontal lobes, and that chronic alcoholics, abstinent for at least a year, will have widespread abnormally low NAc and high Cho, more prominent in frontal than posterior brain regions. 3) To characterize White Matter Hyperintensities (WMHI), which occur with greater frequency in alcoholics than controls. We will develop high-resolution DTI and MRSI acquisition procedures in order to sample multiple diffusion and spectroscopic voxels within WMHIs.